Acetylcholine and norepinephrine released from nerve terminals interact with muscarinic and Beta-adrenergic receptors on the surface of cardiac and pulmonary cells. This interaction mediates the physiological effects of these autonomic neurotransmitters. Muscarinic receptors will be characterized in rat heart and lung using the binding of radioactive agonists and antagonists. Emphasis will be placed on determining if there is more than one subtype of muscarinic binding site. Muscarinic receptor mediated inhibition of GTP-stimulated adenylate cyclase will be characterized in rat heart and lung and these data compared to those obtained in binding studies. Possible changes in cardiac and pulmonary muscarinic and Beta-adrenergic receptors following various pharmacological and physiological manipulations will be investigated. These manipulations are designed to alter the normal autonomic tone on both parasympathetic and sympathetic neurotransmitter receptors. Acetylcholinesterase inhibitors or oxotremorine-M will be used to increase muscarinic tone while desmethylimipramine or isop roterenol will be used to increase adrenergic tone. To decrease muscarinic stimulation, atropine, chlorisondamine and vagotomy will be used. Propranolol, 6-hydroxydopamine, guanethidine and chlorisondamine will be used to decrease sympathetic tone. Following each of these treatments the density and properties of muscarinic and Beta-adrenergic receptors will be measured. Emphasis will be placed on specific changes in Beta1 of Beta2-receptors or on the putative subtypes of muscarinic receptors. If changes occur the regulation of adenylate cyclase activity by the appropriate receptor(s) will be measured and compared to the binding data. These studies may increase our understanding of the biochemical mechanisms underlying the regulation of cardiac and pulmonary function by autonomic neurotransmitters.